Orthotopic Transplantation of dimethylhydrazine (DMH) induced MCA-38 colonic tumor cells into the submucosa of the cecum of C57B1/6J mice results in a "primary" tumor that metastasizes both to the regional mesenteric lymph nodes and to the liver. This provides an animal model that simulates the development, growth and metastasis of human colon cancer and permits an evaluation of the host immune response throughout the natural history of this disease. Throughout the natural history of this disease, the colonic tumor interacts with the immune system at several different levels. During the latency period, initial contact may occur through the local immune system of the gut. As the primary tumor grows, tumor cells may invade the regional mesenteric lymph nodes and the systemic circulation resulting in hepatic metastases. The primary objective of this proposal is to illucidate the role of the local, regional and systemic immune response in this animal model of colon cancer using the in vivo Winn neutralization test. Temporal studies on the development of the local regional and systemic immune response will determine when sensitization occurs in these compartments, the sequence of sensitization between compartments, as well as the dynamic changes in tumor mediated immune responses from the latency period to the appearance of metastasis. The simultaneous presence of residual tumor cells in the gut, regional lymph nodes, and liver offers a unique oppertunity to determine the direct effect of the immune process upon residual tumor cells. The secondary objective of this proposal is to perform further studies with an in vitro micro-leukocyte adherence inhibition (LAI) assay in order to determine if this in vitro assay detects the same immune phenomena as the Winn neutralization test and reflects the biological behavior of the colonic tumor. This project will result in an understanding of the local, regional and systemic immune response during the development, growth and metastasis of colonic tumors. An understanding of this response is essential for the development of new approaches for the detection, treatment and prevention of colon cancer.